Tetrahydropyrane-4: 4-dicarboxylic acid bis-diethylamide



Patented Aug. 17, 1948 UNITED STATES PATENT OFFICE TETRAHYDROPYRAN E-4:4-DICARBOXYLIC ACID BIS-DIETHYLAMIDE Henry Martin and Hans Gysin,Basel, Hans Zaeslin, Riehen, near Basel, and Alfred Margot, Basel,Switzerland, assignors to J. R. Geigy A. G., Basel, Switzerland, a Swissfirm No Drawing. Application October 15, 1943, Serial No. 506,418. InSwitzerland December 18, 1942 1 Claim. (Cl. 260333) ethylorN-cyclohexyl-Z:G-dimethyl piperidine dicarboxylic acid (4:4) and thelike.

The new methylene dicarboxylic acid diamides disubstituted in the amideradical are obtained by causing methylene dicarboxylic acids of theabove definition or functional derivatives thereof, such as for exampletheir halides, esters or anhydrides,

to react with secondary aliphatic or cycloaliphatic amines containingatleast 3 C-atoms or their salts, in the presence or absenceof'solvents, of condensation agents as well as of acid 4:4-dicarboxylicacid bis-diethylamide,which is characterized by its utility as ananaleptic. 1

The present invention is illustrated, but hot limited by the followingexample, wherein the parts are by weight, unless otherwise stated.

EXAMPLE 26.1 parts of tetrahydropyrane-4:4-dicarboxylic acid are treatedwith 63 parts of phosphorus pentachloride. After having stirred themixture over night at room temperature it is heated for a short time to50 C., then distilled in order to separate the phosphorus oxychloride,whereupon the raw acid chloride is dissolved in ether and this solutionallowed to drop in the cold into a solution of 50 parts of diethyl'aminein 200 parts by volume of ether. The diethylamine hydrochloride is thenfiltered off and the filtrate freed from ether and rectified in highvacuo. Boiling point at 0.15 mm.=l53154 C. When recrystallised frompetroleum ether, the compound, tetrahydropyrane-i:4-dicarboxylic acidbis-diethylamicle, melts at 47-48 C.; it is readily soluble in water andether.

'Instead of the tetrahydropyrane compound, the analogous sulfur compoundmay be used quite well; the same is prepared, like the pyrane compound,by means of dichloro diethyl ether from dichloro diethyl sulfide andmalonic ester.

In the following table some further compounds according to the presentinvention may be mentioned:

Table COOH malonic acids R COOH solubility: No. R amine B. P. (mm.) formw=vgfiter CH: (5HO{1\a 1 CzH5N\ C\ HN(OZH5)2 125 0. (0.05) liquidwaeszasilllyfgllhliie r Cfia ride. y CH3 (3H3 /CHOH; 2 E N d1e2-1e3o.(o.oe) -do Do.

OHMJE: do 150-151 C. (0.12) do wlsfiluble, e solue. 3 0 CHCH CHLOE:

CHz.CHz 4 O N-CH CHrO do 158l60 C. (0.25)- 1. do w soluble ashydrochlonde.

CHz.-CH2 CH3 (DH-(RH 5 (3H C-GH=C d0 146-148" C. (0.16)-. solid M. P. w3% soluble, e

\O 3839 G. soluble.

What we claim is: UNITED STATES PATENTS Thetetrahydr0pyrane-4:4-dicarboxylic acid Number Name Date bis-diethyiamideof the formula 697 730 Liebrecht Apr 1902 4.0 0111 1,073,855 HiemenySept, 23, 1913 00 N 1,986,854 Reid Jan. 8, 1935 2,094,608 KritchevskyOct. 5, 1937 I 01115 2,094,609 Kritchevsky Oct. 5, 1937 C 2,109,941DAlelio Mar. 1, 1938 C2115 2,130,523 Carothers Sept. 20, 1932 2,130,948Carothers Sept, 20, 1938 O N 2,084,626 Tabem June 22, 1938 0211.;2,304,475 P001 Dec. 8, 1942 hit t H rd f th w ,3 0,873 Sauer Feb. 9,1943 emg a w e crys a me s01 0 e me mg point 47-48 C. and havinganaleptic activity. FOREIGN PATENTS Number Country DatefifiggYGg/lsifi'l'lN. 400,452 Great Britain Oct, 26, 1933 201,945Sw'tzerland Ma 16, 19 9 HANS ZAESLIN. 1 r 3 ALFRED MARGQT, OTHERREFERENCES REFERENCES CITED 25g.5 (::(1)1em. S0c., pt. 2 (1930),Proceedmgs pp.

The following references are of record in the file of this patent:

Sidgwicks Organic Chemistry of Nitrogen

